Effectiveness of a Community Pharmacy-Based Health Promotion Program on Hypertension in Bangladesh and Pakistan: Study Protocol for a Cluster-Randomized Controlled Trial.

The aim of this multi-country, cluster-randomized trial is to test the impact of pharmacy-based health promotion to reduce the blood pressure of individuals with hypertension over a 12-month period in Bangladesh and Pakistan. The trial will be implemented with two arms. In Bangladesh, the estimated sample size is around 3600 hypertensive patients. In Pakistan, we will select samples equivalent to 10% of the participants from Bangladesh, comprising 360 hypertensive patients from four pharmacies. Community pharmacies will be randomized into one of two parallel groups (allocation ratio 1:1). Pharmacy professionals in the treatment arm will provide their patients with educational training and counseling, as well as phone calls/mobile text messages and care coordination in the health sector, as part of the intervention. The study will be conducted in three phases: a baseline survey with intervention, a midline survey with intervention and follow-up, and an endline survey with impact evaluation. The primary outcome of the study will be BP. The secondary outcomes will be BP controlled to target, treatment adherence, quality of life, mortality or hospital admission rates resulting from hypertension and its related complications, incremental cost per health-related quality of life gained, knowledge on healthy lifestyle and dietary behavior, and change in the prevalence of current smoking status.

Muscle-Protective Effect of Carnosine against Dexamethasone-Induced Muscle Atrophy in C2C12 Myotube.

This study investigated the protective effect of carnosine and its components (L-histidine and ß-alanine [HA]) against dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Myotubes were treated with Dex (10 µM) to induce muscle atrophy manifested by decreased myotube diameter, low myosin heavy chain content, and increased expression of muscle atrophy-associated ubiquitin ligases (Atrogin-1, MuRF-1, and Cbl-b). Carnosine (20 mM) treatment significantly improved the myotube diameter and MyHC protein expression level in Dex-treated C2C12 myotubes. It also downregulated the expression of Atrogin-1, MuRF-1, and Cbl-b and suppressed the expression of forkhead box O3 (FoxO3a) mediated by Dex. Furthermore, reactive oxygen species production was increased by Dex but was ameliorated by carnosine treatment. However, HA (20 mM), the component of carnosine, treatment was found ineffective in preventing Dex-induced protein damage. Therefore, based on above results it can be suggested that carnosine could be a potential therapeutic agent to prevent Dex-induced muscle atrophy compared to its components HA.

CTC together with Shh and Nrf2 are prospective diagnostic markers for HNSCC.

BACKGROUND: The lack of appropriate prognostic biomarkers remains a significant obstacle in the early detection of Head and Neck Squamous Cell Carcinoma (HNSCC), a cancer type with a high mortality rate. Despite considerable advancements in treatment, the success in diagnosing HNSCC at an early stage still needs to be improved. Nuclear factor erythroid 2-related factor 2 (Nrf2) and Sonic Hedgehog (Shh) are overexpressed in various cancers, including HNSCC, and have recently been proposed as possible therapeutic targets for HNSCC. Circulating Tumor Cell (CTC) is a novel concept used for the early detection of cancers, and studies have suggested that a higher CTC count is associated with the aggressiveness of HNSCC and poor survival rates. Therefore, we aimed to establish molecular markers for the early diagnosis of HNSCC considering Shh/Nrf2 overexpression in the background. In addition, the relation between Shh/Nrf2 and CTCs is still unexplored in HNSCC patients. METHODS: In the present study, we selected a cohort of 151 HNSCC patients and categorized them as CTC positive or negative based on the presence or absence of CTCs in their peripheral blood. Data on demographic and clinicopathological features with the survival of the patients were analyzed to select the patient cohort to study Shh/Nrf2 expression. Shh and Nrf2 expression was measured by qRT-PCR. RESULTS: Considering significant demographic [smoking, betel leaf (p-value < 0.0001)] and clinicopathological risk factors [RBC count (p < 0.05), Platelet count (p < 0.05), Neutrophil count (p < 0.005), MCV (p < 0.0001), NLR (p < 0.05), MLR (p < 0.05)], patients who tested positive for CTC also exhibited significant overexpression of Shh/Nrf2 in both blood and tissue compared to CTC-negative patients. A strong association exists between CTCs and tumor grade. Following chemotherapy (a combination of Cisplatin, 5FU, and Paclitaxel), the frequency of CTCs was significantly decreased in patients with HNSCC who had tested positive for CTCs. The Kaplan-Meier plot illustrated that a higher number of CTCs is associated with poorer overall survival (OS) in patients with HNSCC. CONCLUSIONS: Detecting CTCs, and higher expression of Shh and Nrf2 in HNSCC patients' blood, can be a promising tool for diagnosing and prognosticating HNSCC.

Potential of fluorescence fingerprints for fish meat authentication: Differences in freshness evaluation in white and dark meat at frozen state.

As dark meat has a faster deterioration rate and its unintentional mixing occurs during processing, it is crucial to know the status and freshness indicators of dark meat to ensure fishery product quality. In this method, fluorescence fingerprints (FFs) was applied as a rapid and noninvasive quality authentication method to determine differences between white and dark meat in the evaluation of freshness indicators at frozen state. Spotted mackerel (Scomber australasicus) fish chunks with different postmortem conditions (0-40 h ice stored) were obtained and frozen. A new generation of fluorescence spectrophotometer (F-7100) was used to acquire FFs of the frozen fish chunks (containing white and dark meat). Adenosine triphosphate metabolites and pH were determined in both white and dark meat using their relevant biochemical methods. Higher K-values in dark meat might be attributed to a higher accumulation rate of inosine (HxR) in dark meat than in white meat. The pH decrease rate in white meat was higher than that in dark meat during postmortem ice storage periods of fish. Principal component analysis of FFs spectra demonstrated clear discrimination (PC1 + PC2 = 91.7%) between white and dark meat of frozen fish due to the influence of freshness parameters based on the fluorescence features of fish meat. Furthermore, partial least squares regression validation models revealed that freshness indicators of white meat could be predicted more accurately at the frozen state than those of dark meat. This method could be applied during the processing of fishery products, thereby facilitating quality control activities and making it a promising authentication tool for the fisheries industries.

Easy synthesis of PPy/TiO2/ZnO composites with superior photocatalytic performance, efficient supercapacitors and nitrite sensor.

The synthesis of Polypyrrole (PPy)/TiO2/ZnO composites involved a chemical oxidative polymerization process, wherein the addition of TiO2/ZnO was varied from 1 to 10 wt%. The composites' photocatalytic capabilities, supercapacitor performance, and potential use as a nitrite sensor were thoroughly assessed, alongside investigations into their photoluminescence (PL) and morphological characteristics. The strong interaction between TiO2/ZnO and PPy was confirmed using FTIR, UV-Vis, and PL spectroscopy techniques. The composites demonstrated aggregated and spherical-shaped morphological features investigated by FESEM. Such morphological structures of the composites were distinct from the TiO2/ZnO (rod-like) and similar to PPy structure (spherical). However, such composites showed dominating spherical-shaped morphology ensuring a diameter in the range of 50-200 nm. The PPy/TiO2/ZnO composites exhibited significantly enhanced photocatalytic efficiency in methylene blue (MB) removal, achieving a range of 88-93% compared to PPy alone, which only achieved 77.2% MB removal. The Cyclic Voltammetry (CV) data exhibited a promising hybrid supercapacitor performance of the composites with a high capacitance value, good energy density, as well as an excellent power density. The fabricated supercapacitor was capable of lightened up a single red 5 mm LED for a few minutes, indicating the commendable energy storage capacity. A newly developed PPy/TiO2/ZnO composite is potentially used to develop as a sensor probe for the detection of nitrite chemicals using the linear sweep voltammetry (LSV) technique in three electrodes system in room conditions. It is found an excellent sensor results in terms of sensitivity as well as detection limit and satisfactory results when validated with the real samples. These results offer novel insights into the fabrication of PPy/TiO2/ZnO photocatalysts for addressing organic waste treatment, while also presenting promising prospects for potential applications in supercapacitors and sensors.

Evaluation of Population-Level Tobacco Control Interventions and Health Outcomes: A Systematic Review and Meta-Analysis.

Importance: Smoking causes considerable noncommunicable diseases, perinatal morbidity, and mortality. Objective: To investigate the associations of population-level tobacco-control policies with health outcomes. Data Sources: PubMed, EMBASE, Web of Science, Cumulated Index to Nursing and Allied Health Literature, and EconLit were searched from inception to March 2021 (updated on 1 March 2022). References were manually searched. Study Selection: Studies reporting on associations of population-level tobacco control policies with health-related outcomes were included. Data were analyzed from May to July 2022. Data Extraction and Synthesis: Data were extracted by 1 investigator and cross-checked by a second investigator. Analyses were conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Main Outcomes and Measures: The primary outcomes were respiratory system disease (RSD), cardiovascular disease (CVD), cancer, mortality, hospitalization, and health care utilization. The secondary outcomes were adverse birth outcomes, such as low birth weight and preterm birth. Random-effects meta-analysis was used to estimate pooled odds ratios (ORs) and 95% CIs. Results: Of 4952 records identified, 144 population-level studies were included in the final analysis; 126 studies (87.5%) were of high or moderate quality. The most frequently reported policies were smoke-free legislation (126 studies), followed by tax or price increases (14 studies), multicomponent tobacco control programs (12 studies), and a minimum cigarette purchase age law (1 study). Smoke-free legislation was associated with decreased risk of all CVD events (OR, 0.90; 95% CI, 0.86-0.94), RSD events (OR, 0.83; 95% CI, 0.72-0.96), hospitalization due to CVD or RSD (OR, 0.91; 95% CI, 0.87-0.95), and adverse birth outcomes (OR, 0.94; 95% CI, 0.92-0.96). These associations persisted in all sensitivity and subgroup analyses, except for the country income category, for which a significant reduction was only observed in high-income countries. In meta-analysis, there was no clear association of tax or price increases with adverse health outcomes. However, for the narrative synthesis, all 8 studies reported statistically significant associations between tax increases and decreases in adverse health events. Conclusions and Relevance: In this systematic review and meta-analysis, smoke-free legislation was associated with significant reductions in morbidity and mortality related to CVD, RSD, and perinatal outcomes. These findings support the need to accelerate the implementation of smoke-free laws to protect populations against smoking-related harm.

ITGB1BP1, a Novel Transcriptional Target of CD44-Downstream Signaling Promoting Cancer Cell Invasion.

Breast cancer (BC) is the most common malignancy worldwide and has a poor prognosis, because it begins in the breast and disseminates to lymph nodes and distant organs. While invading, BC cells acquire aggressive characteristics from the tumor microenvironment through several mechanisms. Thus, understanding the mechanisms underlying the process of BC cell invasion can pave the way towards the development of targeted therapeutics focused on metastasis. We have previously reported that the activation of CD44 receptor with its major ligand hyaluronan (HA) promotes BC metastasis to the liver in vivo. Next, a gene expression profiling microarray analysis was conducted to identify and validate CD44-downstream transcriptional targets mediating its pro-metastatic function from RNA samples collected from Tet CD44-induced versus control MCF7-B5 cells. We have already validated a number of novel CD44-target genes and published their underlying signaling pathways in promoting BC cell invasion. From the same microarray analysis, Integrin subunit beta 1 binding protein 1 (ITGB1BP1) was also identified as a potential CD44-target gene that was upregulated (2-fold) upon HA activation of CD44. This report will review the lines of evidence collected from the literature to support our hypothesis, and further discuss the possible mechanisms linking HA activation of CD44 to its novel potential transcriptional target ITGB1BP1.

Docosahexaenoic Acid, a Key Compound for Enhancing Sensitization to Drug in Doxorubicin-Resistant MCF-7 Cell Line.

Drug resistance is a well-known and significant obstacle in the battle against cancer, rendering chemotherapy treatments often ineffective. To improve the effectiveness of chemotherapy, researchers are exploring the use of natural molecules that can enhance its ability to kill cancer cells and limit their spread. Docosahexaenoic acid (DHA), a lipid found in marine fish, has been shown to enhance the cytotoxicity of various anti-cancer drugs in vitro and in vivo. While the combined use of chemotherapeutic drugs with DHA demonstrated promising preliminary results in clinical trials, there is still a significant amount of information to be discovered regarding the precise mechanism of action of DHA. As the biological pathways involved in the chemosensitization of already chemoresistant MCF-7 cells are still not entirely unraveled, in this study, we aimed to investigate whether DHA co-treatment could enhance the ability of the chemotherapy drug doxorubicin to inhibit the growth and invasion of MCF-7 breast cancer cells (MCF-7/Dox) that had become resistant to the drug. Upon treating MCF-7/Dox cells with DHA or DHA-doxorubicin, it was observed that the DHA-doxorubicin combination effectively enhanced cancer cell death by impeding in vitro propagation and invasive ability. In addition, it led to an increase in doxorubicin accumulation and triggered apoptosis by arresting the cell cycle at the G2/M phase. Other observed effects included a decrease in the multi-drug resistance (MDR) carrier P-glycoprotein (P-gp) and TG2, a tumor survival factor. Augmented quantities of molecules promoting apoptosis such as Bak1 and caspase-3 and enhanced lipid peroxidation were also detected. Our findings in the cell model suggest that DHA can be further investigated as a natural compound to be used alongside doxorubicin in the treatment of breast cancer that is unresponsive to chemotherapy.

A High Dose of Calcitriol Inhibits Glycolysis and M2 Macrophage Polarization in the Tumor Microenvironment by Repressing mTOR Activation: in vitro and Molecular Docking Studies.

BACKGROUND/AIMS: Macrophages interact with tumor cells within the tumor microenvironment (TME), which plays a crucial role in tumor progression. Cancer cells also can instruct macrophages to facilitate the spread of cancer and the growth of tumors. Thus, modulating macrophages-cancer cells interaction in the TME may be therapeutically beneficial. Although calcitriol (an active form of vitamin D) has anticancer properties, its role in TME is unclear. This study examined the role of calcitriol in the regulation of macrophages and cancer cells in the TME and its influence on the proliferation of breast cancer cells. METHODS: We modeled the TME, in vitro, by collecting conditioned medium from cancer cells (CCM) and macrophages (MCM) and culturing each cell type separately with and without (control) a high-dose (0.5 µM) calcitriol (an active form of vitamin D). An MTT assay was used to examine cell viability. Apoptosis was detected using FITC (fluorescein isothiocyanate) annexin V apoptosis detection kit. Western blotting was used to separate and identify proteins. Quantitative real-time PCR was used to analyze gene expression. Molecular docking studies were performed to evaluate the binding type and interactions of calcitriol to the GLUT1 and mTORC1 ligand-binding sites. RESULTS: Calcitriol treatment suppressed the expression of genes and proteins implicated in glycolysis (GLUT1, HKII, LDHA), promoted cancer cell apoptosis, and reduced viability and Cyclin D1gene expression in MCM-induced breast cancer cells. Additionally, calcitriol treatment suppressed mTOR activation in MCM-induced breast cancer cells. Molecular docking studies further showed efficient binding of calcitriol with GLUT1 and mTORC1. Calcitriol also inhibited CCM-mediated induction of CD206 and increased TNFα gene expression in THP1-derived macrophages. CONCLUSION: The results suggest that calcitriol may impact breast cancer progression by inhibiting glycolysis and M2 macrophage polarization via regulating mTOR activation in the TME and warrants further investigation in vivo.

Reduced IFN-γ levels along with changes in hematologic and immunologic parameters are key to COVID-19 severity in Bangladeshi patients.

The manifestation of coronavirus disease 2019 (COVID-19) severity and mortality has been associated with dysregulation of the immune response, often influenced by racial disparities and conferred by changes in hematologic and immunologic parameters. These biological and hematologic parameters as well as cytokine profiles were investigated in a cohort of 61 COVID-19-positive patients (categorized into mild, moderate, and severe groups) from Bangladesh using standard analytical methods. The data reported that the interleukin (IL)-4 and IL-6 levels were significantly increased, whereas the levels of interferon (IFN)-γ were significantly reduced in patients with severe COVID-19 (p < 0.05) compared with those in patients with mild and/or moderate COVID-19. The extent of erythrocyte sedimentation rate (ESR); neutrophil count; and levels of ferritin, C-reactive protein (CRP), and D-dimer (p < 0.05) were found to be significantly increased, whereas the white blood cell (WBC), lymphocyte, eosinophil, and platelet counts (p < 0.05) were observed to be significantly reduced in patients with severe COVID-19 compared with those in the patients in other 2 groups. Our study exhibited a significantly higher IL-6-to-lymphocyte ratio in patients with severe COVID-19 than in those with mild and moderate COVID-19. The calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and ferritin-to-ESR ratio were significantly increased in patients with severe COVID-19. The increase in the IL-4 and IL-6 levels along with CRP and D-dimer levels may envisage a hyperinflammatory environment and immune dysregulation, which contribute to prolonged viral persistence, leading to severe disease. However, the reduced level of IFN-γ can be attributed to a less fatality toll in Bangladesh compared with that in the rest of the world.

Chitosan-Coated Polymeric Silver and Gold Nanoparticles: Biosynthesis, Characterization and Potential Antibacterial Applications: A Review.

Biosynthesized metal nanoparticles, especially silver and gold nanoparticles, and their conjugates with biopolymers have immense potential in various fields of science due to their enormous applications, including biomedical applications. Polymeric nanoparticles are particles of small sizes from 1 nm to 1000 nm. Among different polymeric nanoparticles, chitosan-coated silver and gold nanoparticles have gained significant interest from researchers due to their various biomedical applications, such as anti-cancer, antibacterial, antiviral, antifungal, anti-inflammatory technologies, as well as targeted drug delivery, etc. Multidrug-resistant pathogenic bacteria have become a serious threat to public health day by day. Novel, effective, and safe antibacterial agents are required to control these multidrug-resistant pathogenic microorganisms. Chitosan-coated silver and gold nanoparticles could be effective and safe agents for controlling these pathogens. It is proven that both chitosan and silver or gold nanoparticles have strong antibacterial activity. By the conjugation of biopolymer chitosan with silver or gold nanoparticles, the stability and antibacterial efficacy against multidrug-resistant pathogenic bacteria will be increased significantly, as well as their toxicity in humans being decreased. In recent years, chitosan-coated silver and gold nanoparticles have been increasingly investigated due to their potential applications in nanomedicine. This review discusses the biologically facile, rapid, and ecofriendly synthesis of chitosan-coated silver and gold nanoparticles; their characterization; and potential antibacterial applications against multidrug-resistant pathogenic bacteria.

Fabrication of porous TiO2 foams by powder metallurgy technique and study of bulk crushing strength for biomedical application.

Despite the importance of porous titanium oxide (PA-TiO2) in diverse functional applications, very little information is available on the compatible mechanical properties for potential biomedical applications. In this study, PA-TiO2 foam was synthesized using space-holding powder metallurgy and sintering methods to produce interconnected opened-cell structure with surface morphology of mountain-like features associated with the extensive rift valley system. Three different types of PA-TiO2 foams with porosities of 35-52% and mean pore diameter of 190-210 µm were fabricated for evaluating the effect of porosity on mechanical properties of bulk PA-TiO2. The modulus of elasticity of PA-TiO2 foams exhibited in the range of 45-262 MPa which was within the range of modulus of elasticity of human cancellous bone. Cytotoxicity test is performed in vitro analysis to observe the effect of cell toxicity to produce osteointegration when used as implantable materials. There was no cytotoxicity effect found and remarkable cell growth was observed for human cancerous (HeLa) cell line. However, there was no cytotoxicity effect found and cell growth was not observed for Vero cell line. This study suggested that PA-TiO2 facilitates cell growth without spreading toxicity and has mechanical properties of cancellous bone. Hence, it has potential application as implant and medical devices in biomedical applications.

Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways.

PURPOSE: This current study investigated the effect of metformin treatment on hepatic oxidative stress and inflammation associated with nonalcoholic fatty liver disease (NADLD) in high fat diet (HFD) fed rats. METHOD: Wistar rats were fed with a HFD or laboratory chow diet for 8 weeks. Metformin was administered orally at a dose of 200 mg/kg. Body weight, food and water intake were recorded on daily basis. Oral glucose tolerance test (OGTT), biochemical analysis and histological examinations were conducted on plasma and tissue samples. Antioxidant and anti-inflammatory mRNA expression was analyzed using reverse transcription polymeric chain reaction (RT-PCR). RESULTS: Metformin treatment for 8 weeks prevented HFD-induced weight gain and decreased fat deposition in HFD fed rats. Biochemical analysis revealed that metformin treatment significantly attenuated nitro-oxidative stress markers malondialdehyde (MDA), advanced protein oxidation product (APOP), and excessive nitric oxide (NO) levels in the liver of HFD fed rats. Gene expression analysis demonestrated that metformin treatment was associated with an enhanced expression of antioxidant genes such as Nrf-2, HO-1, SOD and catalase in liver of HFD fed rats. Metformin treatment also found to modulate the expression of fat metabolizing and anti-inflammatory genes including PPAR--γ, C/EBP-α, SREBP1c, FAS, AMPK and GLUT-4. Consistent with the biochemical and gene expression data, the histopathological examination unveiled that metformin treatment attenuated inflammatory cells infiltration, steatosis, hepatocyte necrosis, collagen deposition, and fibrosis in the liver of HFD fed rats. CONCLUSION: In conclusion, this study suggests that metformin might be effective in the prevention and treatment of HFD-induced steatosis by reducing hepatic oxidative stress and inflammation in the liver.

Mycoremediation of reactive red HE7B dye by Aspergillus salinarus isolated from textile effluents.

Reactive dyes are widely utilized in the textile industry due to their advantageous properties of vivid color, water-fastness, and simple application procedures with minimal energy usage. The toxicity of most azo dyes is a significant environmental concern, as effluents from dye processing and manufacturing sectors are known to be carcinogenic and mutagenic to numerous species. These issues are more grievous in Bangladesh, one of the largest exporters of apparel. This study aimed to isolate and identify potential fungal strains from textile effluent that are capable of degrading Reactive Red HE7B dye (a sulphonated reactive azo dye), a widely used dye in local thread dyeing industries. Dye degradation assay was performed in potato dextrose broth supplemented with 50 mg/l Reactive Red HE7B and the degradation rate was measured by a UV spectrophotometer. DNA extraction, quantification, PCR, internal transcribed spacer (ITS) sequencing, and phylogenetic analysis were performed to identify the selected fungi. Among the isolates, the three best performing strains TEF -3, TEF -4, and TEF -5 showed 97.41%, 93.12%, and 82.89% dye degrading efficacy after 96 h of incubation, respectively. All three strains, TEF-3, TEF-4, and TEF-5 showed similarity with Aspergillus salinarus (accession no. NR_157473.1) and the similarity percentages were 97.02, 96.95, and 95.28 respectively. Interestingly, this study probably the very first indication of textile dye degradation by Aspergillus salinarus strains. Thus, these fungal strains possess the prospectiveness to be utilized in the textile wastewater treatment plants, since the isolates demonstrated the substantial capacity (>80%) to degrade Reactive Red dye after 96 h of incubation.

Tumor-Associated Macrophages as Multifaceted Regulators of Breast Tumor Growth.

Breast cancer is the most commonly occurring cancer in women of Western countries and is the leading cause of cancer-related mortality. The breast tumor microenvironment contains immune cells, fibroblasts, adipocytes, mesenchymal stem cells, and extracellular matrix. Among these cells, macrophages or tumor-associated macrophages (TAMs) are the major components of the breast cancer microenvironment. TAMs facilitate metastasis of the breast tumor and are responsible for poor clinical outcomes. High TAM density was also found liable for the poor prognosis of breast cancer. These observations make altering TAM function a potential therapeutic target to treat breast cancer. The present review summarizes the origin of TAMs, mechanisms of macrophage recruitment and polarization in the tumor, and the contributions of TAMs in tumor progression. We have also discussed our current knowledge about TAM-targeted therapies and the roles of miRNAs and exosomes in re-educating TAM function.

Polyphenol-rich leaf of Aphanamixis polystachya averts liver inflammation, fibrogenesis and oxidative stress in ovariectomized Long-Evans rats.

Aphanamixis polystachya (Wall.) R.Parker, locally known as Pithraj, is a medicinal herb having enormous traditional applications. However, the scientific rationale underlying the ethnomedicinal claims was not well-founded. The current investigation aimed to explore the mechanistic insights of protective effects of ethanol extract of A. polystachya leaf (PT), given orally, on the chemical-intoxicated hepatic inflammation and fibrosis in Long-Evans female overiectomized rats. The GC-MS and HPLC-DAD analysis of PT revealed the presence of several bioactive metabolites, including polyphenolic compounds. Catechin hydrate, caffeic acid, syringic acid, epicatechin and p-coumaric acid have been identified and quantified in the ethanol extract of PT leaf. Intoxication with CCl4 developed the oxidative stress, fibrosis and inflammation in liver of rats. Moreover, thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), advanced protein oxidation product (APOP) level were found increased; whereas superoxide dismutase (SOD) and catalase activities in the plasma and liver were decreased in CCl4 administered rats. Treatment with PT prominently mitigated the oxidative stress (TBARS, NO, APOP), and inflammatory (MPO) markers and improved the endogenous antioxidant enzymes (catalase and SOD) activities in CCl4-intoxicated rats. Additionally, histological assessment confirmed the clear manifestation of inflammation and fibrosis in the liver of CCl4-intoxicated rats, which was prevented by PT and silymarin treatment. In conclusion, PT treatment may protect the liver in CCl4-administered rats, probably by mitigating oxidative stress, inflammation and fibrosis, and also augmenting the function of the antioxidant enzymes.

Etoricoxib treatment prevented body weight gain and ameliorated oxidative stress in the liver of high-fat diet-fed rats.

The main focus of this study was to determine the role of etoricoxib in counterbalancing the oxidative stress, metabolic disturbances, and inflammation in high-fat (HF) diet-induced obese rats. To conduct this study, 28 male Wistar rats (weighing 190-210 g) were distributed randomly into four groups: control, control + etoricoxib, HF, and HF + etoricoxib. After 8 weeks of treatment with etoricoxib (200 mg/kg), all the animals were sacrificed followed by the collection of blood and tissue samples in order to perform biochemical tests along with histological staining on hepatic tissues. According to this study, etoricoxib treatment prevented the body weight gain in HF diet-fed rats. Furthermore, rats of HF + etoricoxib group exhibited better blood glucose tolerance than the rats of HF diet-fed group. In addition, etoricoxib also markedly normalized HF diet-mediated rise of hepatic enzyme activity. Etoricoxib treatment lowered the level of oxidative stress indicators significantly with a parallel augmentation of antioxidant enzyme activities. Furthermore, etoricoxib administration helped in preventing inflammatory cell invasion, collagen accumulation, and fibrotic catastrophe in HF diet-fed rats. The findings of the present work are suggestive of the helpful role of etoricoxib in deterring the metabolic syndrome as well as other deleterious pathological changes afflicting the HF diet-fed rats.

Associations of lifestyle risk factors with overweight or obesity among adolescents: a multicountry analysis.

BACKGROUND: About 35% of the global burden of disease has roots in adolescence. Health in adolescence is an important determinant of health in adulthood. OBJECTIVES: This study aimed to generate risk scores for lifestyle behaviors among adolescents and to estimate the country-specific prevalence of these risk scores. The study also examined the relations of lifestyle risk scores with overweight or obesity among adolescents. METHODS: We used the most recent data available from 20 nationally representative Global School-based Student Health Surveys. Our analytical sample size was 51,597. The outcome of interest was overweight or obesity. We developed 4 lifestyle risk scores (dietary habits, physical activity, sedentary behavior, and tobacco use), which were used as the exposure variables in this study. Multilevel logistic regression models were used to estimate adjusted ORs with 95% CIs. RESULTS: In total, 18.2% of the participants were overweight or obese. Across countries, the percentage of adolescents with unhealthy dietary habits ranged from 76.7% (the Cook Islands) to 94.2% (Timor-Leste), physical inactivity ranged from 47.5% (Bangladesh) to 90.1% (the Philippines), and sedentary behavior ranged from 34.5% (Nepal) to 88.2% (Kuwait). Girls engaged in less physical activity than did boys. Increased odds of overweight or obesity were found among participants with high risk scores for physical inactivity (OR: 1.19; 95% CI: 1.11, 1.27) and for unhealthy sedentary behavior (OR: 1.25; 95% CI: 1.16, 1.35) compared with participants with low risk scores. Girls with high tobacco risk scores had higher odds (OR: 1.30; 95% CI: 1.02, 1.65) of overweight or obesity than did girls with low risk scores for tobacco use, whereas there were no significant differences in risk in boys. CONCLUSIONS: Unhealthy lifestyle behaviors were quite prevalent among adolescents, and higher lifestyle risk scores increased the risk of overweight or obesity.

Canagliflozin ameliorates renal oxidative stress and inflammation by stimulating AMPK-Akt-eNOS pathway in the isoprenaline-induced oxidative stress model.

Diabetes is a leading cause of chronic kidney disease, and the high prevalence of sympathetic nervous system (SNS) hyperactivity in diabetic patients makes them further susceptible to SNS-mediated oxidative stress and accelerated kidney damage. Here, we investigated if canagliflozin can reverse isoprenaline (ISO)-induced renal oxidative damage in rats, a model that mimics SNS overstimulation-induced organ injuries in humans. We found that ISO administration elevates renal oxidative stress markers including malondialdehyde (MDA), advanced protein oxidation product (APOP), myeloperoxidase (MPO) and nitric oxide (NO), while depleting levels of endogenous antioxidants such as catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH). Strikingly, canagliflozin treatment of ISO-treated rats not only prevents elevation of oxidative stress markers but also rescues levels of depleted antioxidants. Our results also show that canagliflozin stimulates antioxidant/anti-inflammatory signaling pathways involving AMP-activated protein kinase (AMPK), Akt and eNOS, and inhibits iNOS and NADPH oxidase isoform 4 (NOX4), all of which are associated with oxidative stress and inflammation. Further, canagliflozin prevents ISO-induced apoptosis of kidney cells by inhibiting Bax protein upregulation and caspase-3 activation. Histological examination of kidney sections reveal that canagliflozin attenuates ISO-mediated increases in inflammatory cell infiltration, collagen deposition and fibrosis. Finally, consistent with these findings, canagliflozin treatment improves kidney function in ISO-treated rats, suggesting that the antioxidant effects may be clinically translatable.

Polyphenolic compounds of amla prevent oxidative stress and fibrosis in the kidney and heart of 2K1C rats.

Amla (Emblica officinalis Gaertn.) is a natural source of antioxidants and possesses valuable medicinal properties. However, the protective effect of amla in the kidney of two-kidneys-one-clip (2K1C) rats has not been explained sufficiently. This study was performed to evaluate the renoprotective effect of amla fruit powder (2.5% W/W) supplementation in kidneys of 2K1C rats. 2K1C rats increased the remnant kidney wet weight and also increased plasma creatinine and uric acid concentration compared to the control. Amla supplementation ameliorates elevated creatinine and uric acid concentration in plasma of 2K1C rats. Various oxidative stress indicators such as malondialdehyde, nitric oxide (NO), and advanced protein oxidation product (APOP) were also increased in plasma, heart, and kidney tissues in 2K1C rats that were also significantly brought down to normal level by amla supplementation. Moreover, the inflammatory cells entry and fibrosis in the 2K1C rat's tissues were prevented by amla supplementation. These research results suggest that amla may restore plasma antioxidant capacities and prevents oxidative stress, inflammation, and fibrosis in 2K1C rats. Taken these results as a base, clinical supplementation of dried amla powder in diet or juice to the CKD patients would be beneficial.